Bladder cancer (BC) is a fatal invasive malignancy accounting for approximately 5% of all cancer deaths in humans; however, the underlying molecular mechanisms and potential targeted therapeutics for BC patients remain unclear. We report herein that RAB14 was overexpressed in BC tissues and cells with high metastatic potential and its abundance was significantly associated with lymph node metastasis (P = 0.001), a high-grade tumor stage (P = 0.009), poor differentiation (P < 0.001) and unfavorable prognoses of BC patients (P = 0.003, log-rank test). Interference by RAB14 mediated a reduction in the TWIST1 protein and inhibited cell migration and invasion (P < 0.05). Moreover, silencing RAB14 reduced cell proliferation and induced apoptosis in vitro and suppressed tumorigenesis in a mouse xenograft model. We demonstrated that RAB14-promoted BC cancer development and progression were associated with activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase signaling through upregulation of MAPK1/MAPK8 and downregulation of dual-specificity protein phosphatase 6/Src homology 2 domain containing transforming protein/Fos proto-oncogene, AP-1 transcription factor subunit (FOS). We provide evidence that RAB14 acts as a tumor promoter and modulates the invasion and metastatic potential of BC cells via activating the MAPK pathway.

Purpose: Bladder cancer (BC) is the most common urinary cancer among men with a high rate of deaths despite the improved medical technology and treatment. Recent evidence demonstrated that Mex-3 RNA-Binding Family Member C (MEX3C) plays various roles in different biological activities, but its molecular mechanisms underlying the pathogenesis of BC remain unclear yet. The aim of this research was to explore the expression patterns of MEX3C and its biological functions in human BC. Materials and methods: The Cancer Genome Atlas (TCGA) and Oncomine databases were jointly used to analyze the expression of MEX3C in BC and its correlation with the clinicopathological features, while real-time PCR and immunohistochemistry analysis were used to verify the predicted results. Wound-healing assay, Matrigel invasion assay, BODIPY staining and Western blot analysis were used in a cell model to assess the effect of MEX3C on the lipid metabolism, invasion and migration of BC and its mechanisms. Results: MEX3C was highly expressed in BC tissues and cells compared with their normal counterparts, and its expression was positively correlated with the clinicopathological features, especially the invasiveness phenotype. Overexpression of MEX3C accumulated lipid droplets and promoted cell adhesion, invasion and migration. We further demonstrated that MEX3C regulated lipid metabolism and promoted tumor development and progression through activation of JNK signaling and upregulating the JNK downstream protein levels of sterol regulatory element-binding proteins-1, fatty acid synthase and acetyl-CoA carboxylase-1. Conclusion: Here we identified MEX3C as a new oncogene to promote bladder tumorigenesis by regulating lipid metabolism through Mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) pathway. These findings suggest a new role of MEX3C in promoting BC tumorigenesis and provide a novel biomarker or molecular target for diagnosis or treating BC.

Docetaxel treatment is a standard chemotherapy strategy for castration-resistant prostate cancer (CRPC), and patients with CRPC eventually develop resistance to treatment. However, little is understood regarding the underlying mechanism of resistance. The present study aimed to identify the underlying crucial genes and regulatory networks associated with docetaxel resistance in prostate cancer using bioinformatics analyses. For this purpose, one expression profile dataset (GSE33455), which included two docetaxel-sensitive and two docetaxel-resistant cell lines, was downloaded from the Gene Expression Omnibus database, and analyses of differential gene expression and function enrichment were performed. A protein-protein interaction (PPI) network was constructed, and the associated hub genes were investigated using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape software. A total of 756 differentially expression genes (DEGs) were identified, including 509 downregulated and 247 upregulated genes. Enrichment analysis revealed that the DEGs were associated with the interferon-γ-mediated signaling pathway, protein binding, bicellular tight junctions and cancer pathways. Two modules were screened from the PPI network, and the corresponding genes were identified to be largely enriched in the interferon-γ-mediated signaling pathway and the negative regulators of the DExD/H-Box helicase 58/interferon induced with helicase C domain 1 signaling pathway, and enriched in cell-cell adhesion and the Rap1 signaling pathway. Among the ten hub genes, epidermal growth factor receptor, spleen tyrosine kinase (SYK), intracellular adhesion molecule 1 (ICAM1), interleukin (IL)6, CXC motif chemokine ligand 8 (CXCL8), cyclin dependent kinase 1 and CD44 molecule (CD44) were significantly differentially expressed in prostate cancer tissues compared with healthy tissues based on The Cancer Genome Atlas data. The Gene Expression Profiling Interactive Analysis database revealed that ICAM1 was positively associated with IL6 and CXCL8, and epidermal growth factor receptor was positively associated with CD44 and SYK. Additionally, ten hub genes, which were identified to be associated with the drug resistance of docetaxel in prostatic carcinoma in the present study, were predominantly associated with tumor progression and metastasis. Reverse transcription-quantitative PCR analysis performed on docetaxel-sensitive and docetaxel-resistant prostate cancer cell lines demonstrated that certain hub genes, including CDK1, 2′-5′-oligoadenylate synthetase 3, CXCL8 and CDH1, were highly expressed in the docetaxel-resistant cell lines, which confirmed the bioinformatics results. In conclusion, the present study identified a number of important genes that are associated with the molecular mechanism of docetaxel resistance by integrated bioinformatical analysis, and these genes and regulatory networks may assist with identifying potential gene therapy targets for CRPC. Further functional analyses are required to validate the...